The functional characteristics of the renal glomerulus have been investigated in Pima Indians of the Gila River Indian Community to identify the underlying pathogenetic mechanisms involved in the initiation and progression of renal disease in non-insulin-dependent diabetes mellitus (NIDDM). The Pima Indian population has a high incidence of NIDDM and diabetic nephropathy. Six groups of subjects were studied: subjects with normal glucose tolerance, individuals with impaired glucose tolerance (IGT), those with newly diagnosed diabetes (<3 years duration NIDDM), and diabetic subjects (greater than or equal to 5 years duration NIDDM) with evidence of (a.) mildly abnormal albumin excretion (b.) severe abnormalities of albumin excretion (c.) normal albumin excretion. Measurements of renal and glomerular capillary wall function including glomerular filtration rate (GFR), renal plasma flow (RFP), dextran sieving coefficients, and albuminuria were performed and correlated. Markers and/or predictors of progression as well as the mechanisms of initiation and progression of diabetic renal disease were sought. Follow-up over a 48 month period has been completed.